本文選題：轉(zhuǎn)化生長(zhǎng)因子-β3 + 骨形成蛋白4�。� 參考：《重慶醫(yī)科大學(xué)》2014年碩士論文

【摘要】：第一部分TGF-β3、BMP4mRNA在TCDD致胎鼠腭裂中的表達(dá) 目的：研究C57BL/6J孕鼠在2,3,7,8-四氯二苯二VA英(2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD)致胎鼠腭裂的最適誘導(dǎo)劑量下，腭突組織中轉(zhuǎn)化生長(zhǎng)因子-β3（transforming growth factor-β3, TGF-β3）和骨形成蛋白4（bone morphogenetic protein4, BMP4）mRNA的表達(dá)情況，并探討其中可能的發(fā)生機(jī)制。 方法：取10只C57BL/6J孕鼠，，隨機(jī)分為T(mén)CDD組（5只）和對(duì)照組（5只），TCDD組于GDl0以TCDD28μg／kg灌胃1次，對(duì)照組于GDl0以等量玉米油灌胃，在GD16.5行大體解剖學(xué)形態(tài)觀察；同時(shí)，使用4%的多聚甲醛固定胎頭，HE染色行組織學(xué)觀察。另取36只孕鼠隨機(jī)分為T(mén)CDD組（18只）和對(duì)照組（18只），在GD13.5、GD14.5和GD15.5（處理方法同前），分別取各組胎鼠腭突組織提取總RNA，利用Q-PCR技術(shù)檢測(cè)各組胎鼠TGF-β3、BMP4mRNA表達(dá)水平。 結(jié)果：在GD16.5，TCDD組胎鼠出現(xiàn)腭裂，對(duì)照組完全正常。在GD13.5、GD14.5和GD15.5，對(duì)照組TGF-β3mRNA相對(duì)表達(dá)量分別為0.7720±0.1548、0.8373±0.2458和0.9475±0.1737，TCDD組分別為1.0948±0.1733、1.1624±0.1892和1.0482±0.3438，TCDD組TGF-β3在GD13.5、GD14.5高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（p＜0.01, p＜0.05）；在GD15.5，TGF-β3亦高于對(duì)照組，差異無(wú)統(tǒng)計(jì)學(xué)意義（p＞0.05）。在GD13.5、GD14.5和GD15.5，對(duì)照組BMP4mRNA相對(duì)表達(dá)量分別為0.8470±0.2168、1.0531±0.0178和0.6865±0.1436，TCDD組分別為1.1114±0.0587、0.8617±0.0780和0.5825±0.1614，TCDD組在GD13.5、GD14.5差異有統(tǒng)計(jì)學(xué)意義（p＜0.05, p＜0.01），在GD15.5差異無(wú)統(tǒng)計(jì)學(xué)意義（p＞0.05）。 結(jié)論：TCDD可穩(wěn)定地致胎鼠腭裂，并可使基因TGF-β3、BMP4mRNA表達(dá)水平發(fā)生顯著性改變。 第二部分組蛋白H3乙�；赥CDD致胎鼠腭裂發(fā)生中的作用 目的：探討組蛋白H3乙酰化在2,3,7,8-四氯二苯二VA英所致的C57BL/6J胎鼠腭裂畸形發(fā)生中可能的作用，及其可能的作用機(jī)制。 方法：將18只C57BL/6J孕鼠隨機(jī)分為T(mén)CDD組和對(duì)照組，每組9只，TCDD組于受孕后第10天(GDl0)以TCDD28μg／kg灌胃1次；對(duì)照組于GDl0以等量玉米油灌胃；分別于GD13.5、GD14.5及GD15.5處死孕鼠，收集胎鼠的上腭組織提取核蛋白，用比色法測(cè)定組蛋白乙酰化酶(histone acetyltransferases, HATs)活性。另選取18只孕鼠隨機(jī)分為T(mén)CDD組和對(duì)照組（分組及處理方法同前），提取上述時(shí)間點(diǎn)各組組織核蛋白，用Western-blot方法檢測(cè)乙�；慕M蛋白H3(Acetylatedhistone H3, Ac-H3)在上腭組織的表達(dá)情況。 結(jié)果：在GD13.5、GD14.5和GD15.5所測(cè)HATs相對(duì)活性O(shè)D值在對(duì)照組分別是0.4097±0.0147、0.5223±0.01709和0.6435±0.0139,TCDD組分別是0.8650±0.0129、0.7191±0.0178和0.5512±0.0168;在GD13.5, GD14.5TCDD組的HATs活性分別高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P㩳0.01);而在GD15.5TCDD組HATs活性低于對(duì)照組，兩組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01)。在GD13.5、GD14.5和GD15.5Ac-H3相對(duì)表達(dá)量對(duì)照組分別是0.7450±0.1135、1.0559±0.2494和1.7955±0.0819, TCDD組分別是1.4490±0.1460、1.6418±0.0997和1.5121±0.1502; TCDD組的Ac-H3表達(dá)在GD13.5、GD14.5分別高于對(duì)照組GD13.5、GD14.5,差異均有統(tǒng)計(jì)學(xué)意義(P0.01, P0.05)；而在GD15.5，TCDD組的Ac-H3表達(dá)低于對(duì)照組，兩組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論：組蛋白H3乙�；瘏⑴c了TCDD所致的C57BL/6J胎鼠腭裂的發(fā)生，可能是TCDD誘導(dǎo)腭裂發(fā)生的機(jī)制之一。
[Abstract]:Part one: expression of TGF- beta 3 and BMP4mRNA in TCDD induced cleft palate of fetal rats
Objective: To study the expression of transforming growth factor - beta 3 (transforming growth factor- beta 3, TGF- beta 3) and bone morphogenetic protein 4 (bone morphogenetic protein4) in C57BL/6J gestation rats with 2,3,7,8- four chloro two benzene two VA English (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) induced cleft palate. Discuss the possible mechanism in it.
Methods: 10 C57BL/6J pregnant rats were randomly divided into TCDD group (5 rats) and control group (5 rats), group TCDD was given 1 times with TCDD28 muon g / kg, and the control group was observed on GDl0 with equal amount of corn oil and observed in GD16.5 on the gross anatomy form. At the same time, 4% polyformaldehyde was used to fix fetal head and HE staining for histological observation. And 36 pregnant rats were randomly divided into two groups. In group TCDD (18) and control group (18 rats), the total RNA was extracted from the palatine process of each group of fetal rats, and the expression level of TGF- beta 3 and BMP4mRNA was detected by Q-PCR technique in GD13.5, GD14.5 and GD15.5.
Results: in GD16.5, TCDD group had cleft palate, and the control group was completely normal. In GD13.5, GD14.5 and GD15.5, the relative expression of TGF- beta 3mRNA in the control group was 0.7720 + 0.1548,0.8373 + 0.2458 and 0.9475 + 0.1737 respectively. The TCDD group was 1.0948 + 0.1733,1.1624 + 0.1892 and 1.0482 + 0.3438 respectively, TCDD group TGF- beta 3 was higher than the control group. There were statistical significance (P < 0.01, P < 0.05), and in GD15.5, TGF- beta 3 was also higher than that in the control group (P > 0.05). In GD13.5, GD14.5 and GD15.5, the relative expression of BMP4mRNA in the control group was 0.8470 + 0.2168,1.0531 + 0.0178 and 0.6865 + 0.1436 respectively. The TCDD group was 1.1114 + + 0.0780 and 0.5825 + 0.1614, respectively. The difference between GD13.5 and GD14.5 was statistically significant (P < 0.05, P < 0.01), and there was no significant difference in GD15.5 (P > 0.05).
Conclusion: TCDD can cause fetal cleft palate in a stable manner, and can significantly change the expression level of TGF- beta 3 and BMP4mRNA.
The role of histone H3 acetylation in the development of cleft palate induced by TCDD in second parts
Objective: To investigate the possible role of histone H3 acetylation in the occurrence of cleft palate in C57BL/6J fetal rats induced by 2,3,7,8- four chloro two benzene two VA and its possible mechanism.
Methods: 18 C57BL/6J pregnant rats were randomly divided into TCDD group and control group, 9 rats in each group. Group TCDD was given 1 times after tenth days of pregnancy (GDl0) with TCDD28 mu g / kg, and the control group was fed with equal amount of corn oil in GDl0. The pregnant rats were killed in GD13.5, GD14.5 and GD15.5, and the upper palate tissues of fetal mice were collected and the protein B was determined by colorimetric method. The activity of histone acetyltransferases (HATs) was selected, and 18 pregnant mice were randomly divided into TCDD and control groups (group and treatment group). The nucleoprotein of each group was extracted at the time point, and the expression of the histone H3 (Acetylatedhistone H3, Ac-H3) in the upper palate tissues was detected by Western-blot.
Results: the relative active OD values of HATs in GD13.5, GD14.5 and GD15.5 were 0.4097 + 0.0147,0.5223 + 0.01709 and 0.6435 + 0.0139 in the control group, and TCDD group was 0.8650 + 0.0129,0.7191 + 0.0178 and 0.5512 + 0.0168 respectively. In GD13.5, the HATs activity of GD14.5TCDD group was higher than that of the control group, and the difference was statistically significant (P? 0.01). The activity of HATs in group DD was lower than that of the control group. The difference between the two groups was statistically significant (P0.01). In GD13.5, the relative expression of GD14.5 and GD15.5Ac-H3 in the control group was 0.7450 + 0.1135,1.0559 + 0.2494 and 1.7955 + 0.0819 respectively. The TCDD group was 1.4490 + 0.1460,1.6418 + 0.0997 and 1.5121 + 0.1502, respectively. The Ac-H3 expression in the TCDD group was higher than that of GD13.5. The control group GD13.5, GD14.5, the difference was statistically significant (P0.01, P0.05), but in GD15.5, TCDD group Ac-H3 expression was lower than the control group, the two groups were statistically significant (P0.05).
Conclusion: histone H3 acetylation is involved in TCDD induced cleft palate in C57BL/6J fetal rats, and may be one of the mechanisms of TCDD induced cleft palate.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R714

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 Charles D.Hebert;STUDY ON THE MECHANISM CELLULAR PROLIFERATION IN HUMAN SQUAMOUS CARCINOMA CELLS BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN(TCDD)[J];癌變.畸變.突變;1991年S1期

2 楊小芳,王沭沂;TCDD及其研究進(jìn)展[J];中國(guó)公共衛(wèi)生;2000年11期

3 ;In vitro Cytotoxicity of TCDD on SPC-A1 Cells[J];Biomedical and Environmental Sciences;2006年01期

4 ;氯化二惡英(TCDD)的毒性[J];黑龍江醫(yī)藥科學(xué);1984年04期

5 曹群立,Chanles D.Helest;TCDD對(duì)人鱗癌細(xì)胞增生機(jī)制的研究[J];癌變.畸變.突變;1991年02期

6 鄒立海;;接觸TCDD工人的癌癥死亡率[J];國(guó)外醫(yī)學(xué)(衛(wèi)生學(xué)分冊(cè));1992年03期

7 GUOYUMEI,WANGSHUYI,WANGXINRU,LASLEYBILL;Effect of TCDD on Maternal Toxicity and Chorionic Gonadotropin──Bioactivity in the Immediate Post-implantation Period of Macaque[J];Biomedical and Environmental Sciences;2000年01期

8 趙玉紅;吳麗霞;趙玉巖;郭磊;;TCDD誘導(dǎo)軟骨細(xì)胞細(xì)胞凋亡的研究[J];沈陽(yáng)醫(yī)學(xué)院學(xué)報(bào);2007年02期

9 黃莉;黃韌;馮媛瑜;劉寒英;丘劍峰;李冰;;2,3,7,8-四氯苯并二VA英(TCDD)短期染毒可造成著床前胚胎丟失并伴隨雌性生殖器官中毒物相關(guān)蛋白的誘導(dǎo)表達(dá)[J];生態(tài)毒理學(xué)報(bào);2010年03期

10 郭玉梅,王沭沂,王心如;TCDD對(duì)獼猴妊娠期及其妊娠結(jié)局的毒性影響[J];中國(guó)公共衛(wèi)生;2000年11期

相關(guān)會(huì)議論文 前10條

1 許先進(jìn);Salvatore Cannistraro;Anna Rita Bizzarri;蘇計(jì)國(guó);陳慰祖;王存新;;TCDD inhibition of the activity of CK2 through binding to the ATP-competitive binding site of the catalytic subunit:Insight from computational studies[A];第五屆全國(guó)生物信息學(xué)與系統(tǒng)生物學(xué)學(xué)術(shù)大會(huì)論文集[C];2012年

2 Hiroki Teraoka;Koji Yamazaki;Yoshikazu Tsujimoto;Tomohiro Imagawa;JohnJ.Stegeman;Richard E.Peterson;Takeo Hiraga;;TCDD induces apoptosis through local circulation failure in midbrain of developing zebrafish[A];中國(guó)藥理學(xué)會(huì)第八次全國(guó)代表大會(huì)暨全國(guó)藥理學(xué)術(shù)會(huì)議論文摘要匯編[C];2002年

3 Hiroki Teraoka;Koji Yamazaki;Yoshikazu Tsujimoto;Tomohiro Imagawa;John J. Stegeman;Richard E. Peterson;Takeo Hiraga;;TCDD induces apoptosis through local circulation failure in midbrain of developing zebrafish[A];中國(guó)藥理學(xué)會(huì)第八次全國(guó)代表大會(huì)論文摘要集（第一部分）[C];2002年

4 ;Effect of Lactational Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)on Growth Development and CYP1A1 Expression of Lungs in Mice Offspring[A];節(jié)能環(huán)保 和諧發(fā)展——2007中國(guó)科協(xié)年會(huì)論文集（二）[C];2007年

5 尹海萍;徐建平;周顯青;;TCDD對(duì)小鼠神經(jīng)神經(jīng)內(nèi)分泌功能的影響及其維生素E的拮抗作用[A];2008年神經(jīng)內(nèi)分泌暨神經(jīng)免疫內(nèi)分泌學(xué)術(shù)研討會(huì)論文摘要匯編[C];2008年

6 馬靜;陳曦;劉亞男;陳京山;冷玲;湯乃軍;;宮內(nèi)TCDD暴露對(duì)成年大鼠血清性激素和睪丸核受體基因表達(dá)的影響[A];中國(guó)毒理學(xué)會(huì)第六屆全國(guó)毒理學(xué)大會(huì)論文摘要[C];2013年

7 Colin R Jefcoate;;TCDD and Wnt3a cooperatively disrupt C3H10T1/2 cell differentiation through restoration of cell adhesion[A];營(yíng)養(yǎng)與慢性病——中國(guó)營(yíng)養(yǎng)學(xué)會(huì)第七屆理事會(huì)青年工作委員會(huì)第一次學(xué)術(shù)交流會(huì)議論文集[C];2010年

8 李承浩;何葦;蒙田;石冰;;小鼠孕期胃飼維生素B6拮抗2,3,7,8,-TCDD誘導(dǎo)的腭裂的實(shí)驗(yàn)研究[A];第七屆全國(guó)唇腭裂學(xué)術(shù)會(huì)議論文集[C];2009年

9 唐志;林樹(shù)海;鄧伶莉;胡傳芹;董繼揚(yáng);蔡宗葦;;TCDD擾亂小鼠肝臟中膽汁酸代謝通路的初步研究[A];第十七屆全國(guó)波譜學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2012年

10 袁秀平;徐盈;吳文忠;黎雯;劉建平;;2,3,7,8-TCDD對(duì)稀有(魚(yú)句)鯽肝臟超微結(jié)構(gòu)影響的研究[A];中國(guó)動(dòng)物科學(xué)研究——中國(guó)動(dòng)物學(xué)會(huì)第十四屆會(huì)員代表大會(huì)及中國(guó)動(dòng)物學(xué)會(huì)65周年年會(huì)論文集[C];1999年

相關(guān)博士學(xué)位論文 前4條

1 黃莉;TCDD的早期妊娠毒性及其機(jī)理研究[D];西北農(nóng)林科技大學(xué);2004年

2 王s

本文編號(hào)：1978773